Cell-adhesion molecules, once believed to function primarily in tethering cells to extracellular ligands, are now recognized as having broader functions in cellular signalling cascades. The CD44 transmembrane glycoprotein family adds new aspects to these roles by participating in signal-transduction processes — not only by establishing specific transmembrane complexes, but also by organizing signalling cascades through association with the actin cytoskeleton. CD44 and its associated partner proteins monitor changes in the extracellular matrix that influence cell growth, survival and differentiation.

CD44: From adhesion molecules to signalling regulators

The Hippo Signaling Pathway in Development and Cancer

Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer.

Identification and characterization of the tuberous sclerosis gene on chromosome 16

A fundamental property of many plasma-membrane proteins is their association with the underlying cytoskeleton to determine cell shape, and to participate in adhesion, motility and other plasma-membrane processes, including endocytosis and exocytosis. The ezrin–radixin–moesin (ERM) proteins are crucial components that provide a regulated linkage between membrane proteins and the cortical cytoskeleton, and also participate in signal-transduction pathways. The closely related tumour suppressor merlin shares many properties with ERM proteins, yet also provides a distinct and essential function.

http://loyce2008.free.fr/MENINGO/Ezrine%20et%20actin/Bretscher,%20erm%20proteins%20integrators%20at%20the%20cell%20cortex,%20Nat%20REv%20CEll%20Biol%202002.pdf

ERM proteins and merlin: integrators at the cell cortex

Neurofibromatosis type 2 (NF2) is a monogenic dominantly inherited disease predisposing carriers to develop nervous system tumours. To identify the genetic defect, the region between two flanking polymorphic markers on chromosome 22 was cloned and several genes identified. One is the site of germ-line mutations in NF2 patients and of somatic mutations in NF2-related tumours. Its deduced product has homology with proteins at the plasma membrane and cytoskeleton interface, a previously unknown site of action of tumour suppressor genes in humans.

Raimund Fashold

Papers

Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2